The administration of antioxidants has been shown to enhance repair and healing processes in cutaneous tissue. Date seed oil (DSO) extract, which might be a potential source of natural antioxidants such as phenols and tocopherols, has been reported to be beneficial in the reduction of chemically induced oxidative stress in normal human skin. In this study, we investigated the protective effects of DSO against hydrogen peroxide (H(2)O(2))-induced oxidative stress in terms of lipid peroxidation, depletion of such endogenous antioxidant defense enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) using normal human epidermal melanocytes (NHEM). The results showed that DSO, endowed with a radical scavenging ability, decreased oxidative injury by inhibition of damage caused by H(2)O(2). Treatment of NHEM with DSO inhibited H(2)O(2)-induced lipid peroxidation. In addition, the extract inhibited H(2)O(2)-induced depletion of antioxidant defense components, such as SOD, CAT, and GPx. Our findings demonstrate that DSO is an efficient extract able to prevent melanocytes oxidative damage induced by H(2)O(2) exposure. Thus it may be a potential promising candidate, as a chemopreventive agent, in the development of melanocyte-related pathologies like vitiligo and melanoma.